James K. Bashkin
Dr. Bashkin received his B.A. in Chemistry from the University of California, Irvine, and his D.Phil. from Oxford, England. He was an NIH postdoctoral fellow at Harvard before joining Monsanto Corporate Research. Dr. Bashkin moved from Monsanto to the Chemistry faculty at Washington University in St. Louis, and subsequently returned to industry at Monsanto (later Pharmacia and Pfizer). He joined the faculty at UMSL in 1999, started the biotech company NanoVir, LLC in 2003 with Chris Fisher, and in 2012 was appointed Professor of Chemistry and Biochemistry.
Office Benton Hall 419
Fax: (314) 516-5342
My group's research has recently been directed to the interface of chemistry and biology, in areas such as "chemical genomics" and the design of antiviral and anticancer agents. Much of this work involves the chemical synthesis and biochemical testing of sequence-specific DNA binding molecules designed to control gene expression. Our main goal is the invention of new chemical methods to treat and diagnose diseases.
Most recently, we have explored bacterial cell-cell communication (quorum sensing), DNA-binding proteins and minor groove-binding polyamides that control of gene expression. As part of this work, we have developed methods for controlling delivery of polyamides to the nucleus of cells, controlling the expression of the COX-2 gene, and inhibiting replication of human papillomavirus (the major cause of cervical cancer).
An earlier stage of our work was concerned with the design of ribozymes mimics: molecules capable of sequence specific cleavage of RNA by the natural transesterification/hydrolysis process. The applications of such molecules include catalytic antisense agents that might greatly enhance the efficiency of the antisense method for destruction of target messenger RNA molecules of biochemical and medicinal importance. We reported the first ribozymes mimic, which is shown schematically in Fig. 1.
The chemical synthesis of the active DNA building block is shown next; ribozymes mimics are constricted by solid-phase synthesis of specific DNA sequences containing the thymidine analog that forms the active site when bound to a divalent metal ion:
In addition to this biological chemistry, I have maintained a strong interest in environmentally-benign organic chemistry, known as Green Chemistry. This work involved developing organic reactions that eliminated toxic waste associated with traditional processes.
Selected Recent Publications
"Correlation of Local Effects of DNA Sequence and Position of Beta-Alanine Inserts with Polyamide-DNA Complex Binding Affinities and Kinetics," S. Wang, R. Nanjunda, K. Aston, J. K. Bashkin and W. Wilson, Biochemistry, 2013 (in press).
"Promoter scanning of the human COX-2 gene with 8-ring polyamides: Unexpected weakening of polyamide–DNA binding and selectivity by replacing an internal N-Me-pyrrole with β-alanine," J. K. Bashkin, K. Aston, J. P. Ramos, K. J. Koeller, R. Nanjunda, G. He, C. M. Dupureur and W. D. Wilson, Biochimie, 2012, available online.
"Fluorescence assay of polyamide-DNA interactions," C. M. Dupureur, J. K. Bashkin, K. Aston, K. J. Koeller, K. R. Gaston and G. He, Analytical Biochem. 2012, 423, 178.
"HPV episome levels are potentially decreased by pyrrole-imidazole polyamindes," T. G. Edwards, K. J. Koeller, U. Slomczynska, K. Fok, M. Helmus, J. K. Bashkin and C. Fisher, Antiviral Res. 2011, 91, 177.
"Compounds Designed to Bind Conserved Regions of Human Papillomavirus (HPV) DNA show Broad-spectrum Activity Against High-risk Genotypes," J. K. Bashkin, T. Edwards, K. Koeller, U. Slomczynska and C. Fisher, Antiviral Res. 2009, 82, A54.
"Effects of Anti-human Papillomavirus (HPV) Disease Agents on HPV Episome Levels In Vitro: Cidofovir, Podophyllotoxin, and Pyrrole–Imidazole Polyamides," T. G. Edwards, K. J. Koeller, J. K. Bashkin and C. Fisher, Antiviral Res. 2009, 82, A68.
"Polyamides for treating human papilloma virus". J. Bashkin, C. Fisher and K. J. Koeller, PCT Int. Appl. 2007, No. 103584, 90pp.
"Electrical signal-activated decontaminating coating, coating application, and articles protected by coatings". P. J. Kinlen, Y. Ding, J. K. Bashkin and S. Hou, Shifeng, U.S. Pat. Appl. Publ. 2007, 20pp.
"Ion-Exchange Chromatography Followed by ESI-MS for Quantitative Analysis of Sugar Monophosphates from Glucose Catabolism," J. J. Walters, M. A. Grayson, M. L. Gross, M. Hughes, G. Shearer, D. H. Kohl and J. K. Bashkin, J. Am. Soc. Mass Spec., 2006, 17, 104.
"Synthesis and evaluation of RNA transesterification efficiency using stereospecific serinol-terpyridine conjugates," W. C. Putnam and J. K. Bashkin, Nucleosides, Nucleotides & Nucleic Acids, 2005, 24, 1309.
"Controlling the intracellular localization of fluorescent polyamide analogs in cultured cells," K. S. Crowley, D. P. Phillion, S. S. Woodard, B. A. Schweitzer, M. Singh, H. Shabany, B. Burnette, P. Hippenmeyer, M. Heitmeier and J. K. Bashkin, Biorg. Med. Chem. Lett., 2003, 13, 1565.
"Structural Analysis of a Bacterial Quorum-Sensing Transcriptional Regulator Complexed with an Autoinducer Pheromone and Operator DNA," R. Zhang, T. Pappas, J. Wronski, N. R. De Lay, P. Miller, T. Oulmassov, J. M. Molyneaux, J. C. Anderson, J. K. Bashkin, S. C. Winans and A. Joachimiak, Nature, 2002, 417, 971.
"Enhancing sequence-specific cleavage of RNA within a duplex region: Incorporation of 1,3-propanediol linkers into oligonucleotide conjugates of serinol-terpyridine," B. N. Trawick, T. A. Osiek, and J. K. Bashkin, Bioconj. Chem. 2001, 12, 900.
"Efficient new ribozyme mimics: direct mapping of molecular design principles from small molecules to macromolecular, biomimetic catalysts," W. C. Putnam, A. T. Daniher, B. N. Trawick and J. K. Bashkin, Nucleic Acids Research, 2001, 29, 2199.
"Probing the Importance of Electrostatic Interactions of Ce(III) with the Phosphodiester Backbone During Transesterification Using Methylphosphonates," T. A. Osiek and J. K. Bashkin, New J. Chem. 2001, 25, 541.